The Genetic Approaches to Cancer Immunotherapy Program is a translational research program dedicated to the conceptualization, development and clinical evaluation of novel immunotherapies that are based on gene transfer and somatic cell engineering. This innovative and highly interactive program brings together investigators with expertise in tumor immunology, transplantation biology, gene transfer biology and noninvasive imaging technologies, who share the common goal of exploring the potential advantages of genetic strategies to treat cancer. Gene transfer into patient cells, transplant donor cells, or engineered auxiliary cells such as antigen-presenting cells, is integral to all projects and supported by the Gene Transfer Core. Multimodality imaging, to study the migration, persistence and activation status of genetically modified cells in vivo, is also preeminent and supported by the Imaging Core. The 3 projects and 3 cores are: 1. Artificial antigen presentation to sensitize virus-specific T cells for adoptive immunotherapy; 2. Genetic approaches to immune adjuvants; 3. Genetic approaches to enhance the anti-tumor functions of T Lymphocytes; Gene Transfer and Somatic Cell Engineering Core ; Imaging Core; Administrative Core. This program integrates scientific discovery, preclinical development, vector production, and patient cell transduction, within a single institution's continuum. This program is the foundation for preclinical and clinical research in genetic medicine and somatic cell engineering at MSKCC. The present revised application is a competitive renewal to continue this research and apply it in the clinical setting. We propose 5 clinical trials that make use of either retroviral-mediated gene transfer or plasmid DNA to genetically modify T lymphocytes or antigen-presenting cells, all of which aim to enhance specific immunity in cancer patients.